Abstract 16970: Low Serum Heat Shock Protein 27 (HSP27) Levels are Predictive of Future Cardiovascular Events and Experimental Vascular Lesions are Prevented or Stabilized with Recombinant HSP27 Therapy
Background: Expression of Heat Shock Protein 27 (HSP27) in human coronary arteries diminishes with progression of atherosclerosis and the extent to which HSP27 over-expression in ApoE-/- mice attenuates atherogenesis is inversely proportional to serum HSP27 levels. However, it is unclear if: i) human HSP27 serum levels are predictive of ischemic events or ii) administering HSP27 either protects from or stabilizes experimental atherosclerotic lesions.
Methods and Results: From July 2006 to February 2008, a cohort of 185 individuals presenting for evaluation of CAD by angiography had serum HSP27 levels measured before follow up (≤5 years). Patients with obstructive CAD at baseline had lower HSP27 levels compared to those free of CAD (p<0.001, Figure A). Consistent with previous murine observations, females had higher HSP27 levels than males (6174.9 ± 746.5-9799.8 (IQR) vs. 2779.0 ± 1129.7-5792.6 (IQR) pg/mL, p=0.049), although in CAD patients HSP27 levels were markedly lower in both sexes. Moreover, low HSP27 levels predicted a combined endpoint of subsequent adverse cardiac events (e.g., MI, stroke, and death; Figure B). To determine if serum HSP27 was causally related to atherogenesis, we administered recombinant HSP27 (rHSP27) to ApoE-/- mice fed an atherogenic diet. rHSP27 therapy reduced the en face lesion area by 31% (p=0.003). Furthermore, administering rHSP27 to mice with established lesions favorably altered both plaque progression (20% decrease en face lesion area, p=0.008) and surrogate markers of plaque stability.
Conclusions: In humans, serum HSP27 levels are diminished in patients with CAD and lower levels are predictive of future cardiovascular events. Administering rHSP27 as a therapy reduces atherosclerotic lesion burden and stabilizes lesions, thereby suggesting that HSP27 may be a novel and treatable biomarker for CAD.
- © 2012 by American Heart Association, Inc.